Clozapine is unique among medications in providing benefit for patients who have poor responses to other antipsychotics. Neurologic toxicity associated with high clozapine levels can occur in patients with infections such as pneumonia or COVID-19, possibly mediated through cytokines or acute phase proteins such as CRP inhibiting clozapine metabolism. The possibility that vaccines could alter CYP1A2 activity and affect clozapine levels will be discussed with reference to a case report of transiently high clozapine levels following SARS-CoV-2 vaccination.

Drug metabolism and disposition can be altered by the innate immune system (IIS), which is the primary clearance pathway for complex drugs (e.g. nanoparticles and biologics). Patients with COVID-19 infections may have altered IIS function and phenotypes, which inhibit the clearance of nanoparticles and biologics and put these patients at higher risk for drug related toxicities. In this talk results from ADME studies conducted in COVID19 patients with characterized IIS profiles will be discussed.

People with highest risk of complications from COVID19 are those with underlying medical conditions (cardiovascular disease, diabetes, hypertension, chronic lung disease) all of which require use of several medicinal agents for maintenance therapy. Approximately one third of those that recover from SARS-CoV-2 infection experience compromised hepatic function, suggesting that potentially long-term alteration of drug metabolism and excretion. This talk will provide an overview of the impact of virus infection and emergency use vaccines on hepatic CYP450 expression and function and will discuss genomic and proteomic signatures collected from animal models of SARS-CoV-2 infection during infection and after recovery.